OBJECTIVE: Persons with human immunodeficiency virus (HIV) have double the risk of developing cardiovascular disease (CVD) compared to the general population. A persistent and heightened immune response to cytomegalovirus (CMV) co-infection may be one contributing factor, but the relationship between CMV replication, virus-specific immune cells and plaque burden is unclear. APPROACH AND RESULTS: We assessed the relationship between CD4(+) T-cell subsets and carotid plaque burden in a cohort of 70 HIV-positive participants with sustained viral suppression on a single antiretroviral regimen and without known CVD. We evaluated relationships between immune parameters, carotid plaque burden, and brachial artery flow-mediated vasodilation (FMD) using multivariable linear and logistic regression models. We found that participants with carotid plaque had increased circulating CX3CR1(+)~GPR56(+)~CD57(+) (i.e., C~G~C)(+) CD4(+) T cells (p=0.03), which is a marker combination associated with anti-viral and cytotoxic responses. In addition, a median of 14.4% [IQR 4.7, 32.7%] of the C~G~C(+) CD4(+) T-cells expressed antigen receptors that recognized a single CMV glycoprotein-B epitope. Notably, using immunofluorescence staining we found that CX3CR1(+) CD4(+) T-cells were present in coronary plaque from deceased HIV-positive persons. C-G-C(+) CD4(+) T cells were also present in cells isolated from the aorta of HIV-negative donors. CONCLUSIONS: HIV-positive persons with carotid atheroma have a higher proportion of circulating CD4(+) T-cells expressing the C~G~C surface marker combination associated with antiviral and cytotoxic responses. These cells can be CMV-specific and are also present in the aorta.
